The goals of this project are as follows: 1) Develop a simple and unique rhesus monkey model for the study of the high intensity stimulation stage through which the human cocaine abuser progresses in the transition from early or recreational use to compulsive use, 2) Evaluate selected drugs such as buprenorphine and buspirone that are believed to be useful in the pharmacotherapy of cocaine abuse, and 3) Test new drugs that are hypothesized to block or suppress the high intensity stimulant effects of The hyperarousal and stimulation produced by an intravenous bolus injection of cocaine in the monkey was termed "rausch" reaction. It mimics, in many respects, the reaction observed in humans after high doses of cocaine. Furthermore, this stage of cocaine use has been virtually ignored by investigators. The model is based on the hypothesis that prevention or interruption of the high intensity stimulation stage will disrupt the binge-relapse cycle, especially, when combined with other therapies including pharmacotherapy during the abstinence phase. Research is intended to characterize fully the syndrome and determine the time course and plasma of half-life cocaine. Plasma levels of cocaine and benzoylecogonine will be measured using GCMS. In addition to testing clinically known drugs with CNS properties, new classes of compounds with unusual and intriguing properties will also be evaluated in this model. They include: 1) the 14-beta substituted cinnamoylaminonormorphinones and their codeinone relatives with partial mu agonist properties. 2) The N-butyrophenone prodine-like compounds with combined neuroleptic opioid properties, 3) the aporphine alkaloids, bulbocapnine, corytuberline, boldine, and glaucine with combined neuroleptic /anticonvulsant /antinociceptive properties and 4) ibogaine, a hallucinogenic psychostimulant. The model will also be available to other investigators for testing of new leads.